Venous Leg UlcerEVRANCT03286140
Early Venous Reflux Ablation Ulcer Trial
A study testing Early endovenous ablation and Delayed endovenous intervention in people with Venous Leg Ulcer, run by Imperial College London at 1 site in United Kingdom.
Trial summary
The EVRA study evaluates the effects of early endovenous ablation on ulcer healing in patients with chronic venous ulceration. Half the patients are randomised to receive early endovenous ablation (within 2 weeks) and half to standard care Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Leg Ulcer
- What is being tested?
- Early endovenous ablation and Delayed endovenous intervention
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 450 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2013to 31 Mar 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Current leg ulceration of greater than 6 weeks, but less than 6 months duration
- Able to give informed consent to participate in the study after reading the patient information documentation
- Patient age > 18 years
- Ankle Brachial Pressure Index (ABPI) ≥ 0.8
- Superficial venous disease on colour duplex assessment deemed to be significant enough to warrant ablation by the treating clinician (either primary or recurrent venous reflux)
Who cannot join
- Presence of deep venous occlusive disease or other conditions precluding superficial venous intervention (at the discretion of local research team)
- Patients who are unable to tolerate any multilayer compression bandaging / stockings will be excluded. However, concordance with compression therapy can be variable for patients at different times. Patients who are generally compliant with compression, but unable to tolerate the bandages for short periods will still be eligible to inclusion. A period of non-compliance with compression bandages will not be considered a protocol violation, but a normal variation within the spectrum of 'standard therapy'.
- Inability of the patient to receive prompt endovenous intervention by recruiting centre
- Pregnancy (female participants of reproductive age will be eligible for inclusion in the study, subject to a negative pregnancy test prior to randomisation)
- Leg ulcer of non-venous aetiology (as assessed by responsible clinician)
- Patient deemed to require skin grafting
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised Clinical Trial to Compare Early Versus Delayed Endovenous Treatment of Superficial Venous Reflux in Patients With Chronic Venous Ulceration
The EVRA study evaluates the effects of early endovenous ablation on ulcer healing in patients with chronic venous ulceration. Half the patients are randomised to receive early endovenous ablation (within 2 weeks) and half to standard care
Read the detailed description
A large number of patients (around 1% of the adult population) suffer from an ulcer (break in the skin surface) near the ankle. In most people, such an injury should heal up within a week or two. However, when there is an underlying problem with the skin, ulcers do not heal and may result in longstanding (chronic), painful, smelly and embarrassing wounds. The ulcers are often due to varicose veins in the legs, which can cause skin breakdown and ulcer formation. To get the ulcer to heal, the current best treatment is to wear a tight compression bandage with multiple layers, with which about 60% of these ulcers will heal within 24 weeks. There is evidence that treatment of the varicose veins by surgery will prevent the ulcer from returning after it has healed. Recent studies have suggested that newer techniques of treating varicose veins, such as injecting a medicine into the varicose vein (sclerotherapy) or treating the vein with heat ablation to seal it (using laser or radiofrequency), in an outpatient setting may help the ulcers to heal more quickly and (like surgery) reduce the chance of the ulcer coming back. These techniques can be carried out in the outpatient setting and are much better tolerated by patients in comparison to surgery. The aim of this study is to see whether early treatment of varicose veins using sclerotherapy or heat ablation helps with healing.
- Conditions
- Venous Leg Ulcer
- Being tested
- Early endovenous ablation, Delayed endovenous intervention
- Keywords
- endovenous ablation
- Medical subject headings
- Varicose Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early endovenous ablationProcedure or surgery
Delayed endovenous interventionProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Standard therapy arm | Active comparator | Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Receives: Procedure: Delayed endovenous intervention |
| Early arm | Experimental | Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Receives: Procedure: Early endovenous ablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Ulcer Healing From Date of Randomisation to Date of Healing up to 365 Days
For the purposes of this study, ulcer healing is defined as complete re-epithelialisation of all ulceration on the randomised (reference) leg in the absence of a scab (eschar) with no dressing required.
Measured: time from date of randomisation to date of healing up to 365 days
Secondary outcomes (9)
Percentage of Participants With Ulcer Healing
Healing rate will be reported at 24 weeks using the percentage of participants with a healed ulcer
Measured: 24 weeks & time to ulcer healing up to 365 days
Ulcer Recurrence / Ulcer Free Time
Will be calculated up to 1 year for each study arm and with the extension, up to 5 years (median approximately 3.7 years). This will allow a very practical and easily understood assessment of the clinical difference between the 2 arms of the study. This will also allow comparison with other studies that have reported this outcome. In order to facilitate accurate calculation of reoccurrence / ulcer free time, clinical follow up will be continued after ulcer healing up to 1 year after randomisation.
Measured: Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years))
Quality Of Life Questionnaire up to 365 Days
Disease specific (AVVQ) quality of life
The Aberdeen Varicose Vein Questionnaire (AVVQ) is a validated patient-reported disease-specific health questionnaire to assess quality of life in patients with varicose veins. The AVVQ comprises a diagram on which patients draw on their varicose veins and a questionnaire with 12 questions, half of which require a response for each leg. The scores range from 0 to 100 (no effect to severe effect).
Measured: 6 weeks post randomisation, 6 months, 12 months
Generic (SF-36) Quality of Life Assessment
Generic (SF-36) quality of life assessment
The Short Form questionnaire-36 items (SF-36) is a generic quality-of-life tool used to determine people's physical and mental health. It has been validated in many patient groups, including those with varicose veins. The physical domain measures physical functioning, physical role limitations, body pain and general health, whereas the mental dimension measures vitality, social functioning, mental health role limitations and general mental health. Two separate scores are produced (separate physical/mental component summary scores), in addition to the eight separate domain scores. Each score is measured on a scale of 0 to 100 (worst to best). Scores represent the percentage of total possible score achieved.
Measured: 6 weeks post randomisation, 6 months, 12 months
EuroQol-5 Dimensions (EQ-5D)
The EuroQol-5 Dimensions (EQ-5D) is a widely recognised, generic tool to measure health outcomes and has been validated in a variety of patient groups, including those with venous leg ulcers. The EQ-5D questionnaire comprises two sections; the first assesses the participant's mobility, self-care, ability to perform usual activities, pain/discomfort and anxiety/depression levels, and the second records the participant's self-rated health on a vertical score of 0 to 100.
Measured: 6 weeks post randomisation, 6 months, 12 months
Health Economic Assessment
A within-RCT cost effectiveness analysis will be carried out based on the data collected in the trial, Resource use items in hospital and community care related to the treatment of venous ulceration or complications will be recorded for each patient at each follow-up. Resource use will be multiplied by UK unit costs obtained from published literature, HRG costs, and manufacturers' list prices to calculate overall costs. A standard tariff will be applied for each bandage change. Utilities (QALYs) will be calculated from the EQ-5D questionnaire administered to patients
Measured: Baseline, 6 weeks, 6 months, 12 months
Clinical Success - Presence of Residual / Recurrent Reflux in the Veins
The presence of residual / recurrent varicose veins remaining on the venous duplex. Any reflux detected by the vascular scientists (as per local scanning policies) is recorded as presence of residual reflux and therefore considered incomplete clinical success. No presence of residual reflux is considered clinical success. (Clinical-Etiology-Anatomy-Pathophysiology) ranges from C0 which means absolutely no venous disease that can be seen or felt in the legs to C6 which means an open and active venous leg ulcer. For this outcome measure: Healed venous leg ulcer (C5), Active venous leg ulcer (C6).
Measured: at 6 weeks
Clinical Success - VCSS
The Venous Clinical Severity Score (VCSS) is a component of the Venous Severity Scoring System designed in 2000 by an ad hoc American Venous Forum committee consensus, in order to compliment the CEAP classification and quantify the severity of disease and subsequent improvement or decline. The VCSS has 10 components (pain, varicose veins, venous oedema, skin pigmentation, inflammation, induration, compression used and active ulcer, duration, number and size), each with four categories assigned values of 0-3. The overall scores can range from 0 (lowest severity) to 30 (highest severity).
Measured: at 6 weeks
Clinical Success - Complications
Number of complications related to the endovenous intervention
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2017
- Study start1 Sep 2013
- Primary completion31 Mar 2019
- Study completion31 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Venous Leg UlcerStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The EVRA ulcer trial is a pragmatic; multicentre randomised clinical trial with participants randomised1:1 to either: 1. 'Standard' therapy consisting of multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) 2. Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard therapy
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 450 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- University of Birmingham, Universidad de Granada, University of Manchester, University of Warwick
- Responsible party
- Sponsor
- Investigators
- Gerard Stansby, Study chair, Newcastle UniversityJulie Brittenden, Study chair, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03286140
- Sponsor's protocol ID
- 13HH0722
- Acronym
- EVRA
- Status last verified
- May 2024
- First submitted
- 4 Sep 2017
- Last updated
- 20 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: At completion of the study, data will be shared in accordance with the NIHR HTA guidance on study outputs as per the research contract between the secretary of state for health research and Imperial College London. Only anonymised data will be shared under the terms of the consent forms. Data and associated documentation will be available to users only under a data-sharing agreement that provides for the following: 1. A commitment to using the data only for research purposes and not to identify any individual participant; 2. A commitment to securing the data using appropriate computer technology; 3. A commitment to destroying or returning the data after analyses are completed. All requests are dealt with on a case-by-case basis. Any request should be submitted to the corresponding author who will then review with the Trial Management Group and sponsor. A record of all access to data will be maintained by the Imperial College Archive team.
Publications
Gohel MS, Mora MSc J, Szigeti M, Epstein DM, Heatley F, Bradbury A, Bulbulia R, Cullum N, Nyamekye I, Poskitt KR, Renton S, Warwick J, Davies AH; Early Venous Reflux Ablation Trial Group. Long-term Clinical and Cost-effectiveness of Early Endovenous Ablation in Venous Ulceration: A Randomized Clinical Trial. JAMA Surg. 2020 Dec 1;155(12):1113-1121. doi: 10.1001/jamasurg.2020.3845.
PubMed 32965493Gohel MS, Heatley F, Liu X, Bradbury A, Bulbulia R, Cullum N, Epstein DM, Nyamekye I, Poskitt KR, Renton S, Warwick J, Davies AH. Early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration: the EVRA RCT. Health Technol Assess. 2019 May;23(24):1-96. doi: 10.3310/hta23240.
PubMed 31140402
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Clinical Trial to Compare Early Versus Delayed Endovenous Treatment of Superficial Venous Reflux in Patients With Chronic Venous Ulceration
- ClinicalTrials.gov ID
- NCT03286140
- Acronym / sponsor ID
- EVRA / 13HH0722
- Conditions
- Venous Leg Ulcer
- Keywords
- endovenous ablation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 450 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- University of Birmingham, Universidad de Granada, University of Manchester, University of Warwick
- Study start
- 1 Sep 2013 (actual)
- Primary completion
- 31 Mar 2019 (actual)
- Study completion
- 31 Mar 2019 (actual)
- First posted
- 18 Sep 2017 (actual)
- Results
- Posted 20 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The EVRA study evaluates the effects of early endovenous ablation on ulcer healing in patients with chronic venous ulceration. Half the patients are randomised to receive early endovenous ablation (within 2 weeks) and half to standard care
Detailed description
A large number of patients (around 1% of the adult population) suffer from an ulcer (break in the skin surface) near the ankle. In most people, such an injury should heal up within a week or two. However, when there is an underlying problem with the skin, ulcers do not heal and may result in longstanding (chronic), painful, smelly and embarrassing wounds. The ulcers are often due to varicose veins in the legs, which can cause skin breakdown and ulcer formation. To get the ulcer to heal, the current best treatment is to wear a tight compression bandage with multiple layers, with which about 60% of these ulcers will heal within 24 weeks. There is evidence that treatment of the varicose veins by surgery will prevent the ulcer from returning after it has healed. Recent studies have suggested that newer techniques of treating varicose veins, such as injecting a medicine into the varicose vein (sclerotherapy) or treating the vein with heat ablation to seal it (using laser or radiofrequency), in an outpatient setting may help the ulcers to heal more quickly and (like surgery) reduce the chance of the ulcer coming back. These techniques can be carried out in the outpatient setting and are much better tolerated by patients in comparison to surgery. The aim of this study is to see whether early treatment of varicose veins using sclerotherapy or heat ablation helps with healing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- The EVRA ulcer trial is a pragmatic; multicentre randomised clinical trial with participants randomised1:1 to either: 1. 'Standard' therapy consisting of multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) 2. Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard therapy
| Arm | Type | Receives |
|---|---|---|
| Standard therapy arm | Active comparator | Procedure: Delayed endovenous interventionMultilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) |
| Early arm | Experimental | Procedure: Early endovenous ablationEarly endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Current leg ulceration of greater than 6 weeks, but less than 6 months duration
- Able to give informed consent to participate in the study after reading the patient information documentation
- Patient age > 18 years
- Ankle Brachial Pressure Index (ABPI) ≥ 0.8
- Superficial venous disease on colour duplex assessment deemed to be significant enough to warrant ablation by the treating clinician (either primary or recurrent venous reflux)
Key exclusion criteria (6 listed)
- Presence of deep venous occlusive disease or other conditions precluding superficial venous intervention (at the discretion of local research team)
- Patients who are unable to tolerate any multilayer compression bandaging / stockings will be excluded. However, concordance with compression therapy can be variable for patients at different times. Patients who are generally compliant with compression, but unable to tolerate the bandages for short periods will still be eligible to inclusion. A period of non-compliance with compression bandages will not be considered a protocol violation, but a normal variation within the spectrum of 'standard therapy'.
- Inability of the patient to receive prompt endovenous intervention by recruiting centre
- Pregnancy (female participants of reproductive age will be eligible for inclusion in the study, subject to a negative pregnancy test prior to randomisation)
- Leg ulcer of non-venous aetiology (as assessed by responsible clinician)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Early endovenous ablation | Procedure or surgery | Early arm |
| Delayed endovenous intervention | Procedure or surgery | Standard therapy arm |
Primary outcome
Time to Ulcer Healing From Date of Randomisation to Date of Healing up to 365 Days
Time frame: time from date of randomisation to date of healing up to 365 days
For the purposes of this study, ulcer healing is defined as complete re-epithelialisation of all ulceration on the randomised (reference) leg in the absence of a scab (eschar) with no dressing required.
9 secondary outcomes
Percentage of Participants With Ulcer Healing
Time frame: 24 weeks & time to ulcer healing up to 365 days
Ulcer Recurrence / Ulcer Free Time
Time frame: Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years))
Quality Of Life Questionnaire up to 365 Days
Time frame: 6 weeks post randomisation, 6 months, 12 months
Generic (SF-36) Quality of Life Assessment
Time frame: 6 weeks post randomisation, 6 months, 12 months
EuroQol-5 Dimensions (EQ-5D)
Time frame: 6 weeks post randomisation, 6 months, 12 months
Health Economic Assessment
Time frame: Baseline, 6 weeks, 6 months, 12 months
Clinical Success - Presence of Residual / Recurrent Reflux in the Veins
Time frame: at 6 weeks
Clinical Success - VCSS
Time frame: at 6 weeks
Clinical Success - Complications
Time frame: up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 32965493Gohel MS, Mora MSc J, Szigeti M, Epstein DM, Heatley F, Bradbury A, Bulbulia R, Cullum N, Nyamekye I, Poskitt KR, Renton S, Warwick J, Davies AH; Early Venous Reflux Ablation Trial Group. Long-term Clinical and Cost-effectiveness of Early Endovenous Ablation in Venous Ulceration: A Randomized Clinical Trial. JAMA Surg. 2020 Dec 1;155(12):1113-1121. doi: 10.1001/jamasurg.2020.3845.
- Results publication: PubMed 31140402Gohel MS, Heatley F, Liu X, Bradbury A, Bulbulia R, Cullum N, Epstein DM, Nyamekye I, Poskitt KR, Renton S, Warwick J, Davies AH. Early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration: the EVRA RCT. Health Technol Assess. 2019 May;23(24):1-96. doi: 10.3310/hta23240.
- Trial websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No. At completion of the study, data will be shared in accordance with the NIHR HTA guidance on study outputs as per the research contract between the secretary of state for health research and Imperial College London. Only anonymised data will be shared under the terms of the consent forms. Data and associated documentation will be available to users only under a data-sharing agreement that provides for the following: 1. A commitment to using the data only for research purposes and not to identify any individual participant; 2. A commitment to securing the data using appropriate computer technology; 3. A commitment to destroying or returning the data after analyses are completed. All requests are dealt with on a case-by-case basis. Any request should be submitted to the corresponding author who will then review with the Trial Management Group and sponsor. A record of all access to data will be maintained by the Imperial College Archive team.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerard Stansby study chair
Newcastle University
Julie Brittenden study chair
University of Glasgow
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Early endovenous ablation and Delayed endovenous intervention in people with Venous Leg Ulcer, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Ulcer Healing From Date of Randomisation to Date of Healing up to 365 Days (time frame: time from date of randomisation to date of healing up to 365 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03286140, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2024.